Hello everyone, I am nisa büyüközkan and today I would like to take this opportunity to talk

to you about HER2 gene defini@on and significance.

First of all I would like to outline the presanta@on,

First I’ll introduce to her2 gene.

Then We’ll take a look at the HER2 protein structure and their func@on.
And I’m going to talk about HER2 overexperssion which is related to the review I wrote
earlier.
I’ll talk about related cancers.
HER2 tes@ng and treatment.
And lastly conclusion.

the human epidermal growth factor receptor 2, or HER2 for short, belongs to a family
of membrane receptor tyrosine kinases (RTKs), which play important roles in cellular
signaling and growth regulation.

The HER2 oncogene is located on chromosome 17q12. HER2 amplifica@on is the primary
pathway of HER2 receptor overexpression and is a major driver of tumor development and
progression in a subset of breast cancers. And other types of cancers

HER2 is just one member of the epidermal growth factor receptor family, alongside
HER1, HER3, and HER4 . These four RTKs are transmembrane single subunit
glycoproteins, each comprising an extracellular ligand-binding domain, a
transmembrane domain, and an intracellular tyrosine kinase catalytic domain. Their
collective presence and interplay contribute to the complex cellular signaling
network.

HER2 is amplified in about 15% to 20% of breast cancers.

The overexpressed HER2 receptor is a valuable therapeu@c target.

Con$nuing with our discussion on HER2, let's delve deeper into the characteris$cs of the
ERBB2 (HER2) protein.The ERBB2 (HER2) protein is composed of a polypep$de chain
consis$ng of a total of 1255 (one thousand 2 hundred fiFy five) amino acids.

The sequence of the HER2 oncogene is homologous to the erb-B oncogene and its 185 kD
phosphoprotein was an@gene@cally related to the epidermal growth factor receptor.

It is worth noting that HER2 receptors dont have a known ligand to form
homodimers. However, they have the ability to form heterodimers with other
members of the HER family.
When this gene is ac@vated it provides the cell with potent prolifera@ve and an@-apoptosis
signals and it is the major driver of tumor development and progression for this subset of
breast cancer. When shown to be overexpressed or amplified by appropriate methods, HER2
is a valuable treatment target.

The dimerization of HER2 receptors leads to the autophosphorylation of tyrosine

residues within their cytoplasmic domain, triggering a multitude of signaling
pathways that ultimately result in cell proliferation and tumorigenesis.

Amplification or overexpression of HER2 occurs in approximately 15–30% of breast

cancers and 10–30% of gastric cancers and serves as a prognostic and predictive
biomarker. HER2 overexpression has also been seen in other cancers like ovary,
endometrium, bladder, lung, colon and head and neck.

Currently, HER2 tes@ng is carried out by several methods: immunohistochemistry (IHC),

fluorescence in situ hybridiza@on (FISH), chromogenic in situ hybridiza@on (CISH), and silver
enhanced in situ hybridiza@on (SISH). These tests are performed on tumor samples that are
fixed in buffered formalin and embedded in paraffin.

HER2 tes@ng results by IHC fall into three categories, posi@ve, equivocal, and nega@ve. Each
of these results guides different approaches in patient management.

In breast cancer, a score of 0 for HER2 staining typically indicates the absence or low
levels of the HER2 protein expression. A score of 0 signifies a notable deficiency or
minimal expression of the HER2/neu protein in cancer cells. In this case, HER2-
targeted therapies are not expected to be effective, and alternative treatment
approaches are generally preferred in the management of breast cancer.

HER2 staining scoring is used as a measure to determine the overexpression of the

HER2/neu protein and assess the options for targeted therapy in breast cancer
patients. Scoring is typically performed on a scale ranging from 0 to 3+, where scores
of 0-1 indicate low expression, 2+ denotes equivocal expression, and a score of 3+
signifies high expression. In cases with a score of 0, it is understood that the
HER2/neu protein is expressed at low levels, and the likelihood of response to
targeted therapies is low.

Okay now we can see 4 different @ssue staining in here. The first one is score 0 and the other
one is score 1 that means the HER2 protein level is low. For score 2 it is equivocal and score 3
staining shows the high expression of HER2. In score 2 or score 3, the HER2-targeted
therapies are expected to be posi@ve and effec@ve.

Trastuzumab, the first FDA-approved drug for HER2-overexpressing cancers,

specifically binds to the external domain of HER2 and selectively targets HER2
proteins involved in the formation of homodimers. Overexpressed HER2 proteins with
protein kinase activity can contribute to tumorigenesis through their auto-
phosphorylation.

Trastuzumab does not inhibit auto-phosphorylation but rather inhibits downstream

signaling of HER2. Like It is indirectly effect to her2 protein

Approximately 25% of cancer patients with HER2 overexpression have shown positive
responses to trastuzumab treatment.

Trastuzumab has shown effective results when used in combination with various
chemotherapeutic drugs.

Examples of drugs commonly used in combination with trastuzumab include

paclitaxel, doxorubicin, and cyclophosphamide. Doxorubicine is the important one
actually.

Additionally, in patients undergoing endocrine therapy, trastuzumab is used in

addition to endocrine treatment if they have both estrogen receptor-positive and
HER2-positive tumors. tumors are different, some can be estrogen positive and her2
positive when estrogen receptor negative and her2 positive.

There are Researchs has demonstrated highly positive responses when trastuzumab is
used after surgical procedures.

Another FDA-approved drug besides trastuzumab is doxorubicin. As known, the HER2

gene located on chromosome 17 is accompanied by the topoisomerase 2 alpha gene,
which is also positioned on chromosome 17.

Doxorubicin, by preventing co-amplification, inhibits the excessive production of

HER2 protein. In addition to its positive outcomes when used alone, combining
doxorubicin with trastuzumab has shown effective results in various variations of the
disease, tailored to the individual patient.
In conclusion, the HER2 gene has emerged as an important gene associated with
various cancer types, including breast cancer, gastric cancer, ovarian cancer, and lung
cancer. Overexpression of the HER2 gene has a significant impact on promoting the
growth, division, and metastasis of cancer cells.

Therefore, targeted therapies that aim to inhibit the overexpression of the HER2 gene,
such as trastuzumab, lapatinib, pertuzumab, and T-DM1, have made significant
advancements in the treatment of HER2-positive cancers.

However, the relationship between the HER2 gene and cancer is still an ongoing area
of research and understanding. Future studies will further enhance our knowledge of
the full impact of the HER2 gene on cancer development and progression, leading to
the development of more effective treatment strategies.

Thank you for your attention and participation.